Day: May 23, 2023

Categories : COVIDTags :

COVID-19: What Next as Shots Expire and Become Harder to Get?

On By ModernMedia

By Adele Baleta for Spotlight

Millions of doses of the Pfizer-BioNtech COVID-19 vaccine procured by the South African government have expired and the shot is largely unavailable to people in the country.

Several people who have contacted Spotlight have expressed “frustration” and “dismay” that despite government having announced in February that it was sitting on a massive stockpile of almost 30 million vaccines, they are struggling to access the Pfizer shot.

Explaining the vast quantity of unused vaccines, the Health Department at the time said vaccine uptake has been low due to decreasing cases, people’s erroneous perception that the pandemic is over, and hesitancy affected by vaccine disinformation.

Expired but not expired?

National Department of Health spokesperson Foster Mohale confirmed that seven million Pfizer doses had expired but they would not be disposed of. Instead, the vaccine manufacturers would test the vaccines to ensure continued safety and efficacy. The South African Health Products Regulatory Authority (SAHPRA) will review the test results and, if satisfied that the vaccine will still work as well as data showed before, they will approve an extended shelf life.

The remaining estimated 23 million Johnson and Johnson (J&J) vaccine doses in South Africa are due to expire in 2024 and 2025.

“The expiry of a vaccine is not the same as the expiry date of food which cannot be extended,” Mohale says, adding that the Pfizer vaccine has a short shelf life and that the vaccine’s expiry date has been extended twice in the past. He says the testing should be done by June and the Pfizer shots would become available in July.

Photo by Mat Napo on Unsplash

A mother from East London, who is hoping to emigrate to the United States, told Spotlight that she was “frantically” trying to get shots for her 12-year-old son in time to leave. In South Africa, none of the currently available COVID-19 vaccines have been authorised for use in children under the age of 16. Elsewhere in the world, for example, in the United States, the Pfizer vaccine has been tested and authorised for use for children from the age of 12. “It is mandatory that he get the vaccine before entering the United States,” she says.

An intern responding to people’s questions on the Department of Health’s hotline says, “Many callers have phoned in stressing about travelling, emigrating, or getting vaccinated for the first time. We have been told that there are very few sites that still have some stock. If people have had two Pfizer doses, they can boost with a J&J dose. However, if they have only had one Pfizer, they will have to wait.”

The public exasperation expressed directly to Spotlight and on social media also relates to the health department’s vaccination website being outdated and it being hard to find places to get vaccinated. As GroundUp reported in January, getting a COVID-19 booster jab is not as easy as it should be.

‘The pandemic is not over’

Referring to the World Health Organization’s (WHO) lifting of the COVID-19 Public Health Emergency of International Concern (PHEIC) on May 5th, Mohale says, “The pandemic is not over and people, especially those who are at highest risk of severe disease and death should get vaccinated.” These included people with co-morbidities and the elderly. He says vaccination for COVID-19 has been integrated into routine primary healthcare facilities, which is where people should go for their jabs.

WHO director-general Tedros Ghebreyesus said it was the end of the emergency phase but not the end of the threat of COVID-19. In the week prior to the announcement, he said the disease claimed a life (globally) every three minutes, “and that’s just the deaths we know about”.

The decision to lift the emergency was based on the decreasing number of deaths and hospitalisations from COVID-19, the high levels of population immunity against SARS-CoV-2, and the widespread availability of COVID-19 vaccines and treatments.

Ghebreyesus warned that the COVID-19 pandemic is not over and that the virus could still pose a serious threat to public health. The WHO has urged countries to continue to monitor the situation closely and to maintain preparedness measures, such as surveillance, testing, and contact tracing.

Some experts have criticised the WHO’s decision to end the emergency phase, arguing that it is premature and could lead to a resurgence of the pandemic. Others have defended the decision, arguing that it is based on the best available evidence and that it is important to give countries the flexibility to manage the pandemic in a way that best suits their own circumstances.

‘Momentous’ announcement

Professor Salim Abdool Kariem, Director of CAPRISA, described the announcement as “momentous”. Writing in his regular COVID-19 updates blog, he says, “… we are still living in the midst of a pandemic with thousands of cases each day. Since SARS-CoV-2 is going to be with us for a long time, a pragmatic decision was needed as the COVID-19 pandemic emergency has been steadily receding and a new variant of concern has not emerged in the last 17 months. But the risk of a new variant of concern is ever-present, even if it is getting progressively smaller with time. The public is also tired of the pandemic and many have simply put it out of sight and out of mind.”

Kariem writes that globally there are currently far more COVID-19 cases, hospitalisations, and deaths each day than we had on the day (30 January 2020) that COVID-19 was initially declared a PHEIC. “So, it (the WHO decision) was not based on the situation getting to a point pre-PHEIC. Waiting to reach that point may take many years or may never happen and so ending the PHEIC is a judgement call, taking many factors into consideration.”

‘Still with us’

Speaking at a recent webinar, hosted by Internews, science writer David Quammen, who wrote a book on COVID-19 called ‘Breathless: The Scientific Race to Defeat a Deadly Virus’ and before that, ‘Spillover’, says, “The coronavirus is still with us, it’s circulating worldwide among humans, and circulating also among whitetail deer, feral mink, and probably other wild mammals.”

He says efforts currently need to be directed to approaching COVID-19 as a long-term cause of human illness, suffering, and death, not “a short-term catastrophe”.

He says laboratory techniques need to be improved as well as manufacturing capacity for updated COVID-19 vaccines. Inequitable access to vaccines will need to be solved. “We will need to dissolve vaccine reluctance and refusal – among the privileged but obdurate, and also among those historically ill-served by Western medicine – with better communication and education.” Diagnostic testing needs to be maintained and not reduced, as well as the sequencing of genomes from patient samples to detect and trace new and immune-evasive variants, he says.

“We will need to prepare, not just for the next coming of SARS-CoV-2 (when it emerges from some infected human, or some deer or mink) but also for the next coronavirus or influenza virus (more than likely H1N1) or other highly adaptive animal-borne virus (there’s a whole rogue’s list of possibilities) that appears in humans, seemingly out of nowhere,” he says. “But they don’t come out of nowhere. They come from nature.”

Republished from Spotlight under a Creative Commons4.0 licence.

Source: Spotlight

Categories : Uncategorized

Sacubitril/Valsartan Shines in HF with Ejection Fraction > 40%

On By ModernMedia

Sacubitril/valsartan leads to greater reduction in plasma NT-proBNP levels compared to valsartan alone after stabilisation for worsening heart failure (HF) in patients with an ejection fraction (EF) above 40%, according to late breaking science presented today at Heart Failure 2023, a scientific congress of the European Society of Cardiology (ESC), and published in the Journal of the American College of Cardiology.

Principal investigator Dr Robert Mentz of Duke University Medical Center, Durham, US said: “These data add to the evidence supporting a potential treatment benefit of sacubitril/valsartan in patients with EF over 40% and particularly in those with EF below normal (< 60%). The findings may influence future guidance for the use of the drug in this population, both in and out of hospital and for those with acute, chronic or de novo heart failure.”

Guidelines recommend consideration of sacubitril/valsartan to reduce hospitalisations in patients with HF with preserved EF (HFpEF; EF >50%) and/or mildly reduced EF (HFmrEF; EF 41–49%). Recommendations differ around the world, with some noting benefits are more evident in those with EF on the lower end of this spectrum (ie below normal).

The PARAGON-HF trial excluded patients with decompensated heart failure, but a post-hoc analysis suggested a larger benefit with sacubitril/valsartan in those recently hospitalised. Whether initiation of sacubitril/valsartan is safe and effective in patients with EF over 40% stabilised after a worsening HF event was unknown. In addition, further data were needed in populations excluded by PARAGON-HF (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m2, systolic blood pressure < 110mmHg, and body mass index [BMI] > 40kg/m2).

PARAGLIDE-HF evaluated the effect of sacubitril/valsartan versus valsartan on changes in NT-proBNP, safety and tolerability in HF patients with EF above 40% who had been stabilised after a worsening HF event. The primary endpoint was the time-averaged proportional change in NT-proBNP from baseline through Weeks 4 and 8. It was chosen to mirror the PIONEER-HF trial, which found that among patients with heart failure with reduced EF (< 40%) who were hospitalised for acute decompensated HF, sacubitril/valsartan led to a greater reduction in NT-proBNP concentration than enalapril.

Patients were recruited from 100 sites in the US and Canada. A total of 466 patients with EF above 40% were enrolled within 30 days of a worsening heart failure event (69% were enrolled while in hospital). The average age was 70 years, 52% were women and 22% were Black. Participants were randomly allocated in a 1:1 ratio to sacubitril/valsartan or valsartan. The time-averaged reduction in NT-proBNP was greater with sacubitril/valsartan compared with valsartan (ratio of change 0.85; p=0.049).

The secondary composite hierarchical outcome consisted of a) time to cardiovascular death, b)number and timing of HF hospitalisations, c) number and timing of urgent HF visits and d) time averaged proportional change in NT-proBNP from baseline to Weeks 4 and 8. This outcome was evaluated using a win ratio analysis, which considers the clinical hierarchy and timing of each component of the endpoint. More serious events are given a higher priority and are analysed first. The hierarchical outcome favoured sacubitril/valsartan (as did each of the components) but was not significant (unmatched win ratio 1.19; 95% CI 0.93–1.52; p=0.16).

Regarding other secondary endpoints, compared with valsartan, sacubitril/valsartan reduced worsening renal function (odds ratio [OR] 0.61). There was more symptomatic hypotension in the sacubitril/valsartan group (OR 1.73). Importantly, subgroup analyses showed evidence of a larger treatment effect in those with EF ≤60% for the change in NT-proBNP (0.78) and the hierarchical outcome (win ratio 1.46).

Dr Mentz said: “PARAGLIDE-HF complements PARAGON-HF by focusing on patients stabilised after a worsening heart failure event with EF above 40% similar to the manner in which PIONEER-HF complemented PARADIGM-HF in patients with reduced EF. PARAGLIDE-HF had no run-in period, allowed both newly diagnosed heart failure and improved EF, included those with acute heart failure without specific echocardiographic requirements and overall had a diverse study population (52% women, 22% Black individuals). The trial also permitted patients with eGFR down to 20 mL/min/1.73m2, systolic blood pressure as low as 100mmHg, and any BMI. The broad and diverse population included in PARAGLIDE-HF supports the generalisability of these data to similar patients seen in routine practice.”

Source: European Society of Cardiology

Categories : Neurodegenerative Diseases VaccinesTags :

Could the BCG Vaccine Reduce Alzheimer’s Risk?

On By ModernMedia
Photo by Mari Lezhava on Unsplash

The Bacillus Calmette-Guérin (BCG) for tuberculosis vaccine has a number additional beneficial effects, and is currently a recommended therapy for non–muscle-invasive bladder cancer. In a new study published in JAMA Network Open, treatment with the BCG vaccine was associated with a reduced risk of Alzheimer’s disease and related dementias.

Although previous research has suggested a link between the BCG vaccine and a lower risk of dementia, studies were limited by size, study design, or analytical methods. To conduct a more robust study, researchers followed 6467 individuals for up to 15 years after they were diagnosed with non–muscle-invasive bladder cancer.

The group included 3388 patients who underwent BCG vaccine treatment and 3079 who served as controls, matched by factors such as age, sex, and medical co-morbidities.

During follow-up, 202 patients in the BCG vaccine group and 262 in the control group developed Alzheimer’s disease and related dementias. The incidence was 8.8 per 1000 person-years and 12.1 per 1000 person-years in the respective groups.

Analyses revealed that treatment with the BCG vaccine was associated with a 20% lower risk of Alzheimer’s disease and related dementias. The protective association was greater in patients aged 70 years or older. Additionally, during follow-up, 751 patients in the BCG vaccine group and 973 in the control group died. Thus, treatment with BCG vaccine was associated with a 25% lower risk of death.

Study leader Marc Weinberg, MD, Ph.D., an Instructor in Psychiatry at MGH, said: “A vaccine like BCG, if proven effective, is a perfect example of a cost-effective, population-health–based solution to a devastating illness like Alzheimer’s disease. We are shifting our focus towards studying the potential benefits of BCG vaccination of older adults in Alzheimer’s disease–related clinical trials.”

If a causal link is found, it will be important to understand the mechanisms involved. Weinberg and his colleagues note that the BCG vaccine’s effects on the immune system may play a role.

Source: Massachusetts General Hospital

Categories : Antibiotics Diseases, Syndromes and ConditionsTags :

Ripping Through Biofilms in Chronic Treatment-resistant Wounds

On By ModernMedia
Methicillin-resistant-Staphylococcus-aureus-MRSA

Researchers have developed a new method that combines palmitoleic acid, gentamicin, and non-invasive ultrasound to help improve drug delivery in chronic wounds that have been infected with Staphylococcus aureus and protected by thick biofilms. Their results were published in Cell Chemical Biology.

Chronic wounds are notoriously challenging to treat because of bacterial infections like S. aureus, which can also be resistant to antibiotics.

To defend itself from the immune system and other threats, S. aureus can band together, creating a slick, slimy biofilm around itself. The biofilm barrier is so thick that neither immune cells nor antibiotics can penetrate through and neutralise the harmful bacteria.

Using a new strategy, researchers at the UNC School of Medicine and the UNC-NC State Joint Department of Biomedical Engineering were able to reduce the challenging MRSA infection in the wounds of diabetic mice by 94%. They were able to completely sterilise the wounds in several of the mice, and the rest had significantly reduced bacterial burden.

“When bacteria are not completely cleared from chronic wounds, it puts the patient at high risk for the infection recurring or of developing a secondary infection,” said senior author Sarah Rowe-Conlon, PhD. “This therapeutic strategy has the potential to improve outcomes and reduce relapse of chronic wound infections in patients. We are excited about the potential of translating this to the clinic, and that’s what we’re exploring right now.”

Biofilms act as a physical barrier to many classes of antibiotics. Virginie Papadopoulou, PhD, was curious to know if non-invasive cavitation-enhanced ultrasound could create enough agitation to form open spaces in the biofilm to facilitate drug-delivery.

Liquid droplets which can be activated by ultrasound, called phase change contrast agent (PCCA), are applied topically to the wound. An ultrasound transducer is focused on the wound and turned on, causing the liquid inside the droplets to expand and turn into microscopic gas-filled microbubbles, when then move rapidly.

The oscillation of these microbubbles agitates the biofilm, both mechanically disrupting it as well as increasing fluid flow. Ultimately, the combination of the biofilm disruption and the increased permeation of the drugs through the biofilm allowed the drugs to come in and kill the bacterial biofilm with very high efficiency.

“Microbubbles and phase change contrast agents act as local amplifiers of ultrasound energy, allowing us to precisely target wounds and areas of the body to achieve therapeutic outcomes not possible with standard ultrasound,” said Dayton. “We hope to be able to use similar technologies to locally delivery chemotherapeutics to stubborn tumours or drive new genetic material into damaged cells as well.”

When the bacterial cells are trapped inside the biofilm, they are left with little access to nutrients and oxygen. To conserve their resources and energy, they transition into a dormant or sleepy state. The bacteria, which are known as persister cells in this state, are extremely resistant to antibiotics.

Researchers chose gentamicin, a topical antibiotic typically ineffective against S. aureus due to widespread antibiotic resistance and poor activity against persister cells. The researchers also introduced a novel antibiotic adjuvant, palmitoleic acid, to their models.

Palmitoleic acid, an unsaturated fatty acid, is a natural product of the human body that has strong antibacterial properties. The fatty acid embeds itself into the membrane of bacterial cells, and the authors discovered that it facilitates the antibiotic’s successful entry into S. aureus cells and is able to kill persistent cells and reverse antibiotic resistance.

Overall, the team is enthusiastic about the new topical, non-invasive approach because it may give scientists and doctors more tools to combat antibiotic resistance and to lessen the serious adverse effects of taking oral antibiotics.

“Systemic antibiotics, such as oral or IV, work very well, but there’s often a large risk associated with them such as toxicity, wiping out gut microflora and C. difficile infection,” said Rowe-Conlon. “Using this system, we are able to make topical drugs work and they can be applied to the site of infection at very high concentrations, without the risks associated with systemic delivery.”

Source: University of North Carolina Health Care

Categories : CancerTags :

Cancer-killing Virus Therapy Shows Promise for Glioblastomas

On By ModernMedia
Photo by Anna Shvets on Pexels

Results of a new clinical trial involving the injection of an oncolytic virus – a virus that targets and kills cancer cells – directly into the tumour, with intravenous immunotherapy shows great promise for patients with glioblastoma according to results published in Nature Medicine.

Drs Farshad Nassiri and Gelareh Zadeh, neurosurgeons at the University Health Network (UHN) in Toronto, found that this novel combination therapy can eradicate the tumour in select patients, with evidence of prolonged survival.

Investigative work by the authors also revealed a new genetic signature within tumour samples that has the potential to predict which patients with glioblastoma are most likely to respond to treatment.

“The initial clinical trial results are promising,” says Dr Zadeh. “We are cautiously optimistic about the long-term clinical benefits for patients.”

Glioblastoma is a notoriously difficult-to-treat primary brain cancer. Despite aggressive treatment, which typically involves surgical removal of the tumour and multiple chemotherapy drugs, the cancer often returns, at which point treatment options are limited.

Immune checkpoint inhibitors are effective treatments for a variety of cancers, but they have had limited success in treating recurrent glioblastoma. This novel therapy involves the combination of an oncolytic virus and immune checkpoint inhibition, using an anti-PD-1 antibody as a targeted immunotherapy.

First, the team zeroed in on the tumour using stereotactic techniques and injected the virus through a small hole and a purpose-built catheter. Then, patients received an anti-PD-1 antibody intravenously, every three weeks, starting one week after surgery.

“These drugs work by preventing cancer’s ability to evade the body’s natural immune response, so they have little benefit when the tumour is immunologically inactive – as is the case in glioblastoma,” explains Dr Zadeh.

“Oncolytic viruses can overcome this limitation by creating a more favourable tumour microenvironment, which then helps to boost anti-tumour immune responses.”

The combination of the oncolytic virus and immune-checkpoint inhibition results in a ‘double hit’ to tumours; the virus directly causes cancer cell death, but also stimulates local immune activity causing inflammation, leaving the cancer cells more vulnerable to targeted immunotherapy.

Dr Zadeh and colleagues evaluated the innovative therapy in 49 patients with recurrent disease, from 15 hospital sites across North America.

UHN, which is the largest research and teaching hospital in Canada and the only Canadian institution involved in the study, treated the majority of the patients enrolled in the trial.

The results show that this combination therapy is safe, well tolerated and prolongs patient survival. The therapy had no major unexpected adverse effects and yielded a median survival of 12.5 months – considerably longer than the six to eight months typically seen with existing therapies.

“We’re very encouraged by these results,” says Dr Farshad Nassiri, first author of the study and a senior neurosurgery resident at the University of Toronto. “Over half of our patients achieved a clinical benefit – stable disease or better – and we saw some remarkable responses with tumours shrinking, and some even disappearing completely. Three patients remain alive at 45, 48 and 60 months after starting the clinical trial.”

“The findings of the study are particularly meaningful as the patients in the trial did not have tumour resection at recurrence – only injection of the virus – which is a novel treatment approach for glioblastoma. So, it’s really remarkable to see these responses,” says Dr Zadeh.

“We believe the key to our success was delivering the virus directly into the tumour prior to using systemic immunotherapy. Our results clearly signal that this can be a safe and effective approach,” adds Dr Nassiri. 

The team also performed experiments to define mutations, gene expression, and immune features of each patient’s tumour. They discovered key immune features which could eventually help clinicians predict treatment responses and understand the mechanisms of glioblastoma resistance.

“In general, the drugs that are used in cancer treatment do not work for every patient, but we believe there is a sub-population of glioblastoma patients that will respond well to this treatment,” says Dr Zadeh. “I believe this translational work, combining basic bench science and clinical trials, is key to moving personalised treatments for glioblastoma forward.”

This is one of the few clinical trials with favourable results for glioblastoma over the last decade, and it was truly a team effort. 

“The trial would not have been possible without our incredible OR teams, research safety teams and researchers – including Dr Warren Mason and his team at Princess Margaret Cancer Centre – and our brave patients and their families. We’re also grateful to the Wilkins Family for providing the funds to enable us to complete trials that advance care for our patients,” says Dr Zadeh. 

The next steps for the group are to test the effectiveness of the combination therapy against other treatments in a randomised clinical trial.

“We are encouraged by these results, but there is still a lot of work ahead of us,” says Dr Nassiri. “Our goal, as always, is to help our patients. That’s what motivates us to continue this research.” 

Source: EurekAlert!